Autism is a pervasive developmental disorder affecting social, communicative, and repetitive behavior domains and cognitive function, and has dramatic impact on quality of life. It is also frequently accompanied by aggression, self-injury, impulsivity, and mood instability, as well as EEG abnormalities and seizure disorders. While large scale studies of childhood autism are currently underway with SSRI's and atypical neuroleptics, little controlled data is available with other agents that might target these core and associated symptoms of autism. This application aims to determine whether there is scientific evidence to support the practice of prescribing divalproex sodium (DS)(valproate) to child/adolescent autistic patients. When a medication is used extensively prior to scientific substantiation in controlled clinical trials, the consequences can sometimes be problematic. Neither the side effects nor efficacy of valproate in treating child/adolescent autistic disorders has been definitively established. Of theoretical interest, valproate has possible neuroprotective effects mediated by signal transduction pathways (i.e., protein kinase-c inhibition and bcl-2 activation) which may potentially be beneficial for a neurodevelopmental disorder such as autism. This study is the first double-blind placebo-controlled medication trial of valproate for children and adolescents with autism, and utilizes a 12-week double-blind placebo-controlled parallel design. The study is unique in examining the treatment effects of valproate (DS) versus placebo on global autism severity; aggression, self-injury and impulsivity; affective instability; repetitive behaviors and social deficits; and functional ability. While our pilot open data evaluating the use of DS for autistic subjects has been encouraging so far (71 percent of autistic subjects were global treatment responders on open DS), a double blind placebo controlled trial with larger sample size and more precise methodology is needed to provide a scientifically sound conclusion about the efficacy, side effects, and effects on functional living skills of this medication in children with autism. This will definitively either support or contradict its widespread use in this understudied and neglected population, and provide a benchmark by which new treatments could be compared. It will also assess the relationship between dose and blood levels and response, potentially identify subgroups particularly responsive to this treatment, and identify which components and associated symptoms are most responsive to change.